[1] In this paper, the conceptual recharge oscillator model for the El Niño-Southern Oscillation phenomenon (ENSO) is utilized to study the influence of fast variability such as that associated with westerly wind bursts (WWB) on dynamics of ENSO and predictability. The ENSO-WWB interaction is simply represented by stochastic forcing modulated by ENSO-related sea surface temperature (SST) anomalies. An analytical framework is developed to describe the ensemble-mean dynamics of ENSO under the stochastic forcing. Numerical ensemble simulations verify the main results derived from the analytical ensemble-mean theory: the state-dependent stochastic forcing enhances the instability of ENSO and its ensemble spread, generates asymmetry in the predictability of the onsets of cold and warm phases of ENSO, and leads to an ensemble-mean bias that may eventually contribute to a climate mean state bias.

The operated lung cancer patients with severe comorbidities were associated with worse survival. The ACCI appears to be a more appropriate prognostic indicator and should be considered for use in clinical practice.

The majority of head and neck squamous cell carcinomas express EGFR, indicating the importance of studying the efficacy of anti-cancer therapy through this pathway. The results also show similar rates of receptor expression in head and neck squamous cell carcinoma patients from our region compared with other parts of the world.

BackgroundStereotactic body radiation therapy (SBRT) has been an emerging non-invasive treatment modality for patients with hepatocellular carcinoma (HCC) when curative treatments cannot be applied. In this study, we report our clinical experience with Cyberknife SBRT for unresectable HCC and evaluate the efficacy and clinical outcomes of this highly sophisticated treatment technology.MethodsBetween 2008 and 2012, 115 patients with unresectable HCC treated with Cyberknife SBRT were retrospectively analyzed. Doses ranged from 26 Gy to 40 Gy were given in 3 to 5 fractions for 3 to 5 consecutive days. The cumulative probability of survival was calculated according to the Kaplan-Meier method and compared using log-rank test. Univariate and multivariate analysis were performed using Cox proportional hazard models.ResultsThe median follow-up was 15.5 months (range, 2-60 months). Based on Response Evaluation and Criteria in Solid Tumors (RECIST). We found that 48.7 % of patients achieved a complete response and 40 % achieved a partial response. Median survival was 15 months (4-25 months). Overall survival (OS) at 1- and 2-years was 63.5 %(54-71.5 %) and 41.3 % (31.6-50.6 %), respectively, while 1- and 2- years Progression-free Survival (PFS) rates were 42.8 %(33.0-52.2 %) and 38.8 % (29.0-48.4 %). Median progression was 6 months (3-16 months). In-field recurrence free survival at 1 and 2 years was 85.3 % (76.2-91.1 %) and 81.6 % (72.2-88.6 %), respectively, while the 1- and 2-years out-field recurrence free survival were 52.5 % (41.2-60.8 %) and 49.5 %(38.9-59.2 %), respectively. Multivariate analysis revealed that Child-Pugh score (A vs. B), Portal vein tumor thrombosis (positive vs. negative), Tumor size (≤4 cm vs >4-9 cm /≥10 cm), and tumor response after SBRT (CR vs. PR/stable) were independent predictors of OS. Acute toxicity was mostly transient and tolerable.ConclusionsCyberknife SBRT appears to be an effective non-invasive treatment for local unresectable HCC with low risk of severe toxicity. These results suggested that Cyberknife SBRT can be a good alternative treatment for unresectable HCC unsuitable for standard treatment.

Purpose: The rationale for hypofractionated radiotherapy in the treatment of prostate cancer is based on the modern understanding of radiobiology and advances in stereotactic body radiotherapy (SBRT) techniques. Whole-pelvis irradiation combined with SBRT boost for high-risk prostate cancer might escalate biologically effective dose without increasing toxicity. Here, we report our 4-year results of SBRT boost for high-risk localized prostate cancer.Methods and Materials: From October 2009 to August 2012, 41 patients newly diagnosed, high-risk or very high-risk (NCCN definition) localized prostate cancer were treated with whole-pelvis irradiation and SBRT boost. The whole pelvis dose was 45 Gy (25 fractions of 1.8 Gy). The SBRT boost dose was 21 Gy (three fractions of 7 Gy). Ninety percent of these patients received hormone therapy. The toxicities of gastrointestinal (GI) and genitourinary (GU) tracts were scored by Common Toxicity Criteria Adverse Effect (CTCAE v3.0). Biochemical failure was defined by Phoenix definition.Results: Median follow-up was 42 months. Mean PSA before treatment was 44.18 ng/ml. Mean PSA level at 3, 6, 12, 18, and 24 months was 0.94, 0.44, 0.13, 0.12, and 0.05 ng/ml, respectively. The estimated 4-year biochemical failure-free survival was 91.9%. Three biochemical failures were observed. GI and GU tract toxicities were minimal. No grade 3 acute GU or GI toxicity was noted. During radiation therapy, 27% of the patient had grade 2 acute GU toxicity and 12% had grade 2 acute GI toxicity. At 3 months, most toxicity scores had returned to baseline. At the last follow-up, there was no grade 3 late GU or GI toxicity.Conclusions: Whole-pelvis irradiation combined with SBRT boost for high-risk localized prostate cancer is feasible with minimal toxicity and encouraging biochemical failure-free survival. Continued accrual and follow-up would be necessary to confirm the biochemical control rate and the toxicity profiles.

Despite recent improvements in the diagnosis and treatment, the final outcomes in patients with nasopharyngeal carcinomas (NPC) still remain suboptimal. Through data mining from published transcriptomic database with further bioinformatic validation, fibronectin (FN1) was identified as a differentially upregulated gene in NPC tissues, which implicates the transition from epithelial to mesenchymal phenotype (EMT) and promotes metastasis. Given the roles of fibronectin in risk stratification and in the frontline therapeutics of common carcinomas, such as renal cell cancer, we explored fibronectin immunoexpression status and its associations with clinicopathological variables and survival in a well-defined cohort of NPC patients. Fibronectin immunohistochemistry was retrospectively performed and analyzed using H-score for 124 biopsy specimens from NPC patients who received standard treatment without distant metastasis at initial diagnosis. Those cases with H-score higher than the median value were regarded as fibronectin overexpression. The findings were correlated with clinicopathological variables, EBV latent membrane protein 1 (LMP1) expression, disease-specific survival (DSS), distant metastasis-free survival (DMFS), and local recurrence-free survival (LRFS). Fibronectin overexpression was significantly associated with American Joint Committee on Cancer (AJCC) stages III-IV (p = 0.019) and LMP1 expression (p = 0.004), and univariately predictive of adverse outcomes for DSS, DMFS, and LRFS (all p < 0.0001). In the multivariate comparison, fibronectin overexpression still remained prognostically independent to portend worse DSS (p < 0.01, hazard ratio = 5.958), DMFS (p < 0.01, hazard ratio = 5.728), and LRFS (p < 0.01, hazard ratio = 5.411) together with a vanced AJCC stages III-IV. Fibronectin is upregulated in a subset of NPCs, and its increased immunoexpression significantly correlated with advanced features, justifying the potentiality of fibronectin as a theragnostic biomaker of NPC.

Withaferin A (WFA) has been reported to inhibit cancer cell proliferation based on high cytotoxic concentrations. However, the low cytotoxic effect of WFA in regulating cancer cell migration is rarely investigated. The purpose of this study is to investigate the changes in migration and mechanisms of oral cancer Ca9-22 cells after low concentrations of WFA treatment. WFA under 0.5 μM at 24 h treatment shows no cytotoxicity to oral cancer Ca9-22 cells (~95% viability). Under this condition, WFA triggers reactive oxygen species (ROS) production and inhibits 2D (wound healing) and 3D cell migration (transwell) and Matrigel invasion. Mechanically, WFA inhibits matrix metalloproteinase (MMP)-2 and MMP-9 activities but induces mRNA expression for a group of antioxidant genes, such as nuclear factor, erythroid 2-like 2 (NFE2L2), heme oxygenase 1 (HMOX1), glutathione-disulfide reductase (GSR), and NAD(P)H quinone dehydrogenase 1 (NQO1)) in Ca9-22 cells. Moreover, WFA induces mild phosphorylation of the mitogen-activated protein kinase (MAPK) family, including extracellular signal-regulated kinases 1/2 (ERK1/2), c-Jun N-terminal kinase (JNK), and p38 expression. All WFA-induced changes were suppressed by the presence of ROS scavenger N-acetylcysteine (NAC). Therefore, these results suggest that low concentration of WFA retains potent ROS-mediated anti-migration and -invasion abilities for oral cancer cells.

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